Pharm - Lecture 8 - Adrenergic antagonists Flashcards
What is the mechanism of adrenergic neuron blockers?
drugs that disrupt the synthesis, storage or release of norepinephrine
Which drugs are Adrenergic neuron blockers? (3)
1) Guanethidine
2) Guanadrel
3) Reserpine
What is the mechanism of Guanethidine and Guanadrel? (2)
Inhibits norepinephrine release and depletes neuronal amine stores
What is the therapeutic use of Guanethidine and Guanadrel?
Severe hypertension
What is the difference between Guanethidine and Guanadrel?
Guanethidine is a polar compound that does not enter the CNS
How are Guanethidine and Guanadrel taken up into the cell?
NET - therfore they are inhibited by tricyclic antidepressants that inhibit NET
What are the side effects of Guanethidine and Guanadrel?
Many side effects: orthostatic hypotension, interferes with sexual function, diarrhae, muscle weakness, edema
What is the mechanism of Reserpine?
It inhibits he vesicular monamine oxidase transporter 2 (VMAT2) therby inhibiting the synthesis of norepinephrine
How does Reserpine get into the cell?
diffusion (does not need VMAT2)
What is the therapeutic use of Reserpine?
treats essential hypertension - rarely used
What are the side effects of Reserpine?
Many CNS side effects, depression, suicide, sedation
Other side effects: diarrhae, orthostaic hypo-tension, increased gastric acid secretion
What is Reserpine’s length of onset and how long does it last?
Slow onset and Long acting
What is the mechanism of adrenergic receptor blockers?
Agents produce their major actions by inhibiting alpha and beta receptors. Both exogenously administered as well as endogenously released catecholamines are blocked
What drugs are alpha adrenergic receptor antoganists? (4)
1) Phenoxybenzamine
2) Phentolamine
3) Prazosin
4) Tamsulosin
Which receptors does Phenoxybenzamine and Phentolamine block?
a1 and a2
What is the mechanism of Phenoxybenzamine?
Irreversible antagonist via covalent bonding with receptor. New receptors need to be synthesized, so it is very long lasting
What is the effect of Phenoxybenzamine?
produces vasodilation proportional to the degree of sympathetic tone
What is the mechanism of phentolamine?
Competitive reversible antagonist
Block can be overcome by increasing the agonist
What is the therapeutic use of Phenoxybenzamine? (2)
1) pheochromocytoma
2) To reverse or shorten the duration of soft-tissue anesthesia produced by combined local anesthetic and sympathomimetic
What is the therapeutic use of Phentolamine? (3)
1) hypertension
2) pheochromocytoma
3) to reverse or shorten the duration of soft tissue anesthesia produced by combined local anesthetic and sympathomimetic
What are the side effects of phenoxybenzamine and phentolamine? (2)
1) tachycardia and salt/water retention (edema)
2) Orthostatic hypotension
What is the mechanism of Prazosin? How is it administered?
orally active - competitive blocker of a1 receptors
What is the effect of Prazoisn?
1) minimal tachycardia
2) decreases vascular tone in resistance (arterioles) and capacitance (veins)
3) produce favorable lipid profile: low LDL, high HDL
Why is reflex tachcardia less problamatic with Prazosin?
Prazosin doesn’t block the pre-synpatic a2 receptors very much
What are the major therapeutic uses of Prazosin?
1) hypertension
2) short-term treatment of congestive heart failure (because of preload and afterload reducing agent)
3) Benign prostatic hyperplasia (BPH) - relaxes a1 mediated contraction of prostate and bladder neck that contributes to resistance to urine flow
What are the side effects of prazosin?
1) “first dose” phenomenon - hypotension and syncope 30-90 minutes after first dose
2) presistent orthostatic hypotension
3) salt and water retention (edema)
What is the mechanism and receptor selectivty for Tamsulosin?
a1 receptor antagonist with ome selectivity for a1A versus a1B (favors a1A receptor blockage in prostate)
What is the therapeutic use of Tamsulosin?
Effective for treatement of BPH with little effect on blood pressure
Not approved for treatmenet of hypertension
What are the non-selective beta adrenergic receptor antagonists?
1) Propranolol
2) Timolol
3) Metoprolol
4) Atenolol
What is the mechanism and receptor specificty of Propranolol?
Competitive reversible blockade of both B1 and B2 receptors
What are the therapeutic uses of Propanolol? (5)
Hypertension
Angina
cardiac arrhythmias due to excess catecholamines or that respond to a reduction in heart rate/AV conduction velocity
Acute myocardial infarction
migraine prophylaxis
What are the side effects of Propranolol? (4)
Cardiac depression, bradycardia/heart block
May increase airway resistance
Mask sympoms of hypoglycemia
sedation, impotence, nightmares
What types of patients should you be warry about giving Propranolol to? (6)
Patients with:
Asthma
CHF
bradyarrhythmias, AV block
insulint-dependentdiabetes prone to hypoglycemic episodes
hypotension
vasopastic angina
What is the mechanism for Timolol?
Non-selective beta receptor antagonist?
What is the therapeutic use of Timolol?
Similar to propranolol along with treatment of wide angle glaucoma
What is the mechanism of Metoprolol?
Competitive, reversible B1 receptor blocker (low doses it is more selective at blocking the B1 receptor)
What is the therapeutic use of metoprolol?
Similar to propranolol - also used to treate heart failure
What is the mechanism of Atenolol?
B1 receptor antagonist
What is the therapeutic use of Atenolol?
Similar to propranolol (except for migraine prophylaxis)
What is the mechanism of Labetalol?
Competitive antagonist of a1 receptor and both B receptors (non-selective)
What is the therapeutic use of Labetalol?
Essential hypertension and hypertensive emergencies
What is the mechansim of Carvedilol?
Competitive antagonist of a1 receptor and both B receptors (non-selective)
What is the effect of Carvedilol? (2)
1) anti-oxidant properties and anti-inflammatory effects
2) blocks L-type calcium channels at higher doses
What is the therapuetic use of Carvedilol? (3)
1) CHF
2) Hypertension
3) Acute MI
